The overall objectives of the proposed research are to determine the genetic interrelationships among the various animal and human influenza virus strains and to elucidate the mechanisms involved in the production of influenza variants, which have led to the current existence of a very large number of diverse influenza strains. Studies on the genetic relatedness of field isolates of animal and human influenza strains should allow correlations to be made between biological activities, such as host range and virulence with specific genome RNA sequences. The analyses of the mutation frequency of individual antigenic sites on the influenza hemagglutinin will tell us what factors affect the mutation rate of the virus and how they influence its unique ability to change rapidly. In addition, a concerted effort will be made to detect intragenic recombinants to determine if this powerful mechanism for the generation of "new" genetic information is available to the influenza virus.